Cinchona villosa can be generally recognized by its rather small, thin-textured leaves with well developed petioles and at least some soft spreading pubesscence below and rather sharp tips, along with its rather small flowers with the corolla tube 6-9 mm long. Andersson (1998) diagnosed this species as always having pit domatia on the leaves, but the leaves of some specimens annotated by him (e.g., Palacios et al. 8493) sometimes have domatia that match his illustration (1998: fig. 4A-B) of the other form of domatia he recognized and contrasted, tufted domatia.

This species is quite similar to Cinchona calisaya, which occurs naturally apparently from central Peru through Bolivia, and C. villosa apparently replaces the closely related C. calisaya north of its range. Cinchona calisaya can be separated by its leaves that are stiffer in texture and its generally larger flowers, with the corolla tube 8-13 mm long. Andersson (1998) also noted that C. villosa is similar to C. glandulifera, and these are found in the same region; C. glandulifera can be separated by its stiff-textured leaves with quite short petioles and its smaller flowers, with the corolla tube 5-5.5 mm long. Also similar is C. micrantha, which differs in its smaller white flowers, with the corolla tube 5-7.5 mm long.

Relatively few specimens were available to Andersson; with more collections now available Cinchona villosa can be seen to range to central Bolivia, and to vary somewhat morphologically. Some plants from southern Ecuador and adjacent Peru, the range originally described by Andersson, have relatively small regularly elliptic leaves, while other plants have significantly larger, broadly elliptic to obovate leaves. These larger-leaved plants are found from southern Ecuador to Bolivia; the plants of central Peru through Bolivia match plants of northern Peru included by Andersson in C. villosa.